This study will look at a method of hormonal birth control, called the NuvaRing, and specific anti-HIV medications, called antiretrovirals (ARVs). Some studies of women who use a hormonal birth control method (specifically oral pills, patches, and injections) and take ARVs have shown that ARVs interact with the hormones released by the birth control medication. These interactions may cause the birth control to be less effective at preventing pregnancy. There is also concern that hormonal birth control can increase HIV spreading to others, but more studies are needed to determine if this is true. The investigators do not know whether the NuvaRing and ARVs interact when they are used together, so this study will look to see if certain ARVs (efavirenz and atazanavir/ritonavir) interact with the two hormones released by NuvaRing. This will help us to determine if NuvaRing is safe and effective for women with HIV infection who are taking ARVs. The study will also include HIV-infected women who are not on ARVs but will use the NuvaRing to show us what the hormone levels are like in a similar group of women not on ARVs.

Vaginal rings are also currently being studied to deliver anti-HIV medications that may prevent HIV acquisition, and to provide birth control over a longer period of time (more than 1 month). Since vaginal rings will become more commonly used to administer medications, the investigators want to better understand the potential for drug interactions with drugs given vaginally. This study will also help us understand the potential for drug interactions between ARVs given orally, and other drugs given through vaginal rings, like the NuvaRing. Additionally, this study will help us understand how hormones released from a vaginal ring affect the amount of HIV virus in the genital tract, the bacterial make-up (microbiome) of the female genital track, and the immune system within the genital tract, all of which may affect the chances of spreading HIV.

Etonogestrel and ethinyl estradiol concentrations at study day 21 [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Etonogestrel and ethinyl estradiol concentrations obtained at study day 21 (before the vaginal ring is removed) from participants enrolled in all three study arms.

Secondary Outcome Measures:

Etonogestrel and ethinyl estradiol concentrations obtained on study days 7 and 14 after vaginal ring administration in all three study arms [ Time Frame: Study days 7 and 14 after vaginal ring administration ] [ Designated as safety issue: No ]

AUC(0-24h) defines area under the concentration-time curve over the doing period of 24 hours; Cmin defines minimum concentration in the dosing period of 24 hours; Cmax defines maximum concentration in the dosing interval of 24 hours; Tmax defines time to maximum concentration since dose is initiated; CL/F defines apparent oral clearance.

Any signs and symptoms of grade 2 or higher related to vaginal ring exposure from individual participants enrolled in all of the three study Arms A, B, and C [ Time Frame: Signs and symptoms are assessed during the weekly visits on study days 7, 14 and 21 ] [ Designated as safety issue: Yes ]

NuvaRing is made of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate, is latex free, and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. NuvaRing has an outer diameter of 54 mm and a cross-sectional diameter of 4mm. Once NuvaRing is inserted into the vagina, the ring should remain in place (not be removed) continuously for 3 weeks (21 days). After being in place for the first 21 days of the study, the ring may be removed after the day 21 study visit evaluations have been completed.

Other Name: NuvaRing

Experimental: NuvaRing with EFV plus ≥2 NRTIs

Device: Etonogestrel/ethinyl estradiol vaginal ring (NuvaRing)

NuvaRing is made of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate, is latex free, and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. NuvaRing has an outer diameter of 54 mm and a cross-sectional diameter of 4mm. Once NuvaRing is inserted into the vagina, the ring should remain in place (not be removed) continuously for 3 weeks (21 days). After being in place for the first 21 days of the study, the ring may be removed after the day 21 study visit evaluations have been completed.

Other Name: NuvaRing

Drug: Efavirenz

Participants will receive EFV 600 mg daily with two or more NRTIs

Other Name: EFV

Experimental: NuvaRing with ATV/r plus TDF and ≥1 NRTIs

Device: Etonogestrel/ethinyl estradiol vaginal ring (NuvaRing)

NuvaRing is made of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate, is latex free, and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. NuvaRing has an outer diameter of 54 mm and a cross-sectional diameter of 4mm. Once NuvaRing is inserted into the vagina, the ring should remain in place (not be removed) continuously for 3 weeks (21 days). After being in place for the first 21 days of the study, the ring may be removed after the day 21 study visit evaluations have been completed.

Participants must be receiving either 1) EFV 600 mg daily with 2 or more NRTIs, 2) ATV/r 300 mg/ 100 mg daily with TDF 300 mg and 1 or more additional NRTIs, or 3) no ART. ART regimens should be stable for 30 days prior to study entry with no plans to change therapy during the first 28 days of this study. Participants receiving no ART should have no plans to initiate ART during the first 28 days of the study.

NOTE: Participants must have access to their ART regimens through their primary care providers. ART medications are not supplied by this study.

For participants on ART, documentation of plasma HIV-1 RNA </= 400 copies/mL obtained within 60 days prior to study entry.

For participants not on ART, CD4+ cell count must be ≥350 cells/mm3, obtained within 60 days prior to study entry.

Last menstrual period </=6 months prior to study entry. If last menstrual period >6 months prior to study entry without another cause for amenorrhea, such as recent pregnancy, serum follicle-stimulating hormone (FSH) must be checked and be </= 40 mIU/mL to be eligible for enrollment.

Premenopausal females with at least one functioning ovary.

Documentation of Pap smear within 1 year prior to study entry.

Negative serum or urine-HCG pregnancy test with a sensitivity of ≤25 mIU/mL within 60 days prior to study entry and within 24 hours prior to study entry

All participants must agree not to participate in a conception process (eg, active attempt to become pregnant or in vitro fertilization) for the duration of the study. Because it is unknown if ARVs will adversely affect the efficacy of NuvaRing as a contraceptive method, participants of reproductive potential, who are participating in sexual activities that could lead to pregnancy, must agree to use an additional reliable form of contraception while in the study. Acceptable additional methods of contraception include:

Condoms (male or female) with or without a spermicidal agent

Non-hormonal intrauterine device (IUD)

Other hormonal forms of contraception are not allowed during the study period.

Condoms should be used to prevent transmission of HIV and sexually transmitted diseases between sexual partners.

NOTE: Participants with bilateral tubal ligation or non-hormonal IUD may be enrolled.

Use of any prohibited medications within 30 days prior to study entry.

Initiated, discontinued, or changed doses of drugs that are CYP substrates or known to have drug interactions with ethinyl estradiol or etonogestrel within 30 days prior to study entry.

Bilateral oophorectomy.

For women older than 35 years of age, smoking 15 or more cigarettes per day.

History of invasive cancer of the reproductive tract; known or suspected malignancy of the breast, or known increased risk for breast cancer; undiagnosed abnormal vaginal bleeding; liver tumors; or serious ocular disorders at any time prior to study entry.

Chronic immunosuppressive conditions other than HIV.

Use of systemic or inhaled corticosteroids such as for acute therapy for Pneumocystis pneumonia (PCP) or asthma exacerbation and prednisone ≥10 mg (or equivalent) for any reason other than a stable or tapering dose.

History of deep venous thrombosis or pulmonary embolism.

History of cerebral vascular or coronary artery disease.

Severe uncontrolled hypertension within 60 days prior to study entry.

Diabetes with vascular involvement.

Clinically active cervical or vaginal infection at study entry. NOTE: Gonorrhea, chlamydia, and trichomonas testing will be performed during screening using techniques available at the local sites and documented in source documentation and case report forms (CRFs). Testing for bacterial vaginosis, performed using techniques available at the local sites, is only necessary if the participant is symptomatic and the provider feels treatment may be necessary. Women with genital herpes lesions should wait to be screened until the herpetic lesions have healed.

Acute infections or other opportunistic diseases requiring medication within 14 days prior to study entry.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01903031